Multimodality Imaging Markers of Adverse Myocardial Remodeling in Aortic Stenosis

Aortic stenosis (AS) causes left ventricular remodeling (hypertrophy, remodeling, fibrosis) and other cardiac changes (left atrial dilatation, pulmonary artery and right ventricular changes). These changes, and whether they are reversible (reverse remodeling), are major determinants of timing and outcome from transcatheter or surgical aortic valve replacement. Cardiac changes in response to AS afterload can either be adaptive and reversible, or maladaptive and irreversible, when they may convey residual risk after intervention. Structural and hemodynamic assessment of AS therefore needs to evaluate more than the valve, and, in particular, the myocardial remodeling response. Imaging plays a key role in this. This review assesses how multimodality imaging evaluates AS myocardial hypertrophy and its components (cellular hypertrophy, fibrosis, microvascular changes, and additional features such as cardiac amyloid) both before and after intervention, and seeks to highlight how care and outcomes in AS could be improved

Edge-Based Compartmental Modeling for Infectious Disease Spread Part III: Disease and Population Structure

We consider the edge-based compartmental models for infectious disease spread introduced in Part I. These models allow us to consider standard SIR diseases spreading in random populations. In this paper we show how to handle deviations of the disease or population from the simplistic assumptions of Part I. We allow the population to have structure due to effects such as demographic detail or multiple types of risk behavior the disease to have more complicated natural history. We introduce these modifications in the static network context, though it is straightforward to incorporate them into dynamic networks. We also consider serosorting, which requires using the dynamic network models. The basic methods we use to derive these generalizations are widely applicable, and so it is straightforward to introduce many other generalizations not considered here

Improved Exercise-Related Skeletal Muscle Oxygen Consumption Following Uptake of Endurance Training Measured Using Near-Infrared Spectroscopy

Skeletal muscle metabolic function is known to respond positively to exercise interventions. Developing non-invasive techniques that quantify metabolic adaptations and identifying interventions that impart successful response are ongoing challenges for research. Healthy non-athletic adults (18–35 years old) were enrolled in a study investigating physiological adaptations to a minimum of 16 weeks endurance training prior to undertaking their first marathon. Before beginning training, participants underwent measurements of skeletal muscle oxygen consumption using near-infrared spectroscopy (NIRS) at rest (resting muscleV˙O2) and immediately following a maximal exercise test (post-exercise muscleV˙O2). Exercise-related increase in muscleV˙O2 (ΔmV˙O2) was derived from these measurements and cardio-pulmonary peakV˙O2 measured by analysis of expired gases. All measurements were repeated within 3 weeks of participants completing following the marathon and marathon completion time recorded. MuscleV˙O2 was positively correlated with cardio-pulmonary peakV˙O2 (r = 0.63, p < 0.001). MuscleV˙O2 increased at follow-up (48% increase; p = 0.004) despite no change in cardio-pulmonary peakV˙O2 (0% change; p = 0.97). Faster marathon completion time correlated with higher cardio-pulmonary peakV˙O2 (rpartial = −0.58, p = 0.002) but not muscleV˙O2 (rpartial = 0.16, p = 0.44) after adjustment for age and sex [and adipose tissue thickness (ATT) for muscleV˙O2 measurements]. Skeletal muscle metabolic adaptions occur following training and completion of a first-time marathon; these can be identified non-invasively using NIRS. Although the cardio-pulmonary system is limiting for running performance, skeletal muscle changes can be detected despite minimal improvement in cardio-pulmonary function

Identification of a new member of the phage shock protein response in Escherichia coli, the phage shock protein g (PspG)

The phage shock protein operon (pspABCDE) of Escherichia coli is strongly up-regulated in response to overexpression of the filamentous phage secretin protein IV (pIV) and by many other stress conditions including defects in protein export. PspA has an established role in maintenance of the proton-motive force of the cell under stress conditions. Here we present evidence for a new member of the phage shock response in E. coli. Using transcriptional profiling, we show that the synthesis of pIV in E. coli leads to a highly restricted response limited to the up-regulation of the psp operon genes and yjbO. The psp operon and yjbO are also up-regulated in response to pIV in Salmonella enterica serovar Typhimurium. yjbO is a highly conserved gene found exclusively in bacteria that contain a psp operon but is physically unlinked to the psp operon. yjbO encodes a putative inner membrane protein that is co-controlled with the psp operon genes and is predicted to be an effector of the psp response in E. coli. We present evidence that yjbO expression is driven by sigma(54)-RNA polymerase, activated by PspF and integration host factor, and negatively regulated by PspA. PspF specifically regulates only members of the PspF regulon: pspABCDE and yjbO. We found that increased expression of YjbO results in decreased motility of bacteria. Because yjbO is co-conserved and co-regulated with the psp operon and is a member of the phage shock protein F regulon, we propose that yjbO be renamed pspG

Planning intervention using dynamic assessments: A case study

Dynamic assessments (DA) of language have been shown to be a useful addition to the battery of tests used to diagnose language impairments in children, and to evaluate their skills. The current article explores the value of the information gained from a DA in planning intervention for a child with language impairment. A single case study was used to demonstrate the detailed qualitative information that can be derived from a DA procedure, and how that information may be used to elicit greater gains from intervention. The participant was a boy, aged 9, with a previously diagnosed language impairment. He was receiving language therapy regularly in a language resource base attached to his school. The CELF-3(UK) was used to monitor changes in his language, before and after two periods of intervention. The initial baseline phase consisted of regular ongoing language therapy. The second phase of therapy was modified by the speech and language therapist after receiving a report of the child’s performance on the Dynamic Assessment of Sentence Structure (DASS; Hasson et al., 2012), and observations of the child’s metalinguistic and metacognitive awareness. Greater gains observed in the second phase of therapy reflected the good modifiability shown by the child’s performance on the DASS

Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.

BackgroundM2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages.MethodsMycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm2. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.ResultsThe ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm3) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).ConclusionsDietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC

Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land

There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1–2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population

Sex Dimorphism in the Myocardial Response to Aortic Stenosis

OBJECTIVES: The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. BACKGROUND: AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. METHODS: This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. RESULTS: In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro-brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). CONCLUSIONS: CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471.)

Media justice: Madeleine McCann, intermediatization and "trial by media" in the British press

Three-year-old Madeleine McCann disappeared on 3 May 2007 from a holiday apartment in Portugal. Over five years and multiple investigations that failed to solve this abducted child case, Madeleine and her parents were subject to a process of relentless ‘intermediatization’. Across 24–7 news coverage, websites, documentaries, films, YouTube videos, books, magazines, music and artworks, Madeleine was a mediagenic image of innocence and a lucrative story. In contrast to Madeleine’s media sacralization, the representation of her parents, Kate and Gerry McCann, fluctuated between periods of vociferous support and prolonged and libellous ‘trial by media’. This article analyses how the global intermediatization of the ‘Maddie Mystery’ fed into and fuelled the ‘trial by media’ of Kate and Gerry McCann in the UK press. Our theorization of ‘trial by media’ is developed and refined through considering its legal limitations in an era of ‘attack journalism’ and unprecedented official UK inquiries into press misconduct and criminality